Jarman E R, Tan K A L, Lamb J R
Immunobiology Group, MRC Centre for Inflammation Research, Respiratory Medicine Unit, University of Edinburgh Medical School, Edinburgh, UK.
Clin Exp Allergy. 2005 Jul;35(7):960-9. doi: 10.1111/j.1365-2222.2005.02284.x.
Current studies on mechanisms underlying allergen-induced pulmonary inflammation and asthma are hampered by the lack of appropriate physiological in vivo models that reflect the natural route of allergen exposure and sensitization.
To generate and phenotype a transgenic mouse strain expressing the T cell receptor (TCR) specific for an immunodominant domain of the major inhalant allergen Dermatophagoides pteronyssinus species of house dust mite (Der p 1), for the development of an in vivo model of allergic asthma.
Der p 1 transgenic mice were generated using TCR-alphabeta derived from a CD4+ T cell hybridoma reactive with Der p 1 residues p 110-131. The frequency and functional activity of peripheral T cells were determined and parameters of airway inflammation assessed following allergen challenge of the airways with Der p 1.
CD4+ T cells are functionally active, exhibiting dose-dependent proliferation and IL-4 production on primary stimulation with Der p 1 or Der p 1, p 110-131 in vitro, independent of in vivo antigen priming. On sensitization of the airways with allergen, in the absence of systemic priming or the application of adjuvants, the TCR transgenic mice develop airway inflammation characterized by a marked lymphocytic and eosinophilic infiltrate with goblet cell hyperplasia and enhanced mucin production.
The Der p 1 TCR transgenic mice provide a model for investigating the pathophysiological mechanisms of pulmonary inflammation following sensitization by exposure of the airways to allergen and for investigating the mode of action and efficacy of novel immunotherapeutics.
目前关于变应原诱导的肺部炎症和哮喘潜在机制的研究因缺乏能反映变应原暴露和致敏自然途径的合适的体内生理学模型而受阻。
构建并鉴定一种表达针对主要吸入性变应原屋尘螨（Der p 1）免疫显性结构域的T细胞受体（TCR）的转基因小鼠品系，用于建立过敏性哮喘的体内模型。
利用来自与Der p 1残基p 110 - 131反应的CD4⁺T细胞杂交瘤的TCR - αβ构建Der p 1转基因小鼠。测定外周T细胞的频率和功能活性，并在用Der p 1对气道进行变应原激发后评估气道炎症参数。
CD4⁺T细胞功能活跃，在体外初次用Der p 1或Der p 1、p 110 - 131刺激时表现出剂量依赖性增殖和IL - 4产生，与体内抗原致敏无关。在用变应原致敏气道时，在没有全身致敏或应用佐剂的情况下，TCR转基因小鼠会发生气道炎症，其特征为明显的淋巴细胞和嗜酸性粒细胞浸润、杯状细胞增生以及粘蛋白产生增加。
Der p 1 TCR转基因小鼠为研究气道暴露于变应原后致敏引起的肺部炎症的病理生理机制以及研究新型免疫疗法的作用方式和疗效提供了一个模型。
